Management of Phenylketonuria: Current and Future Perspectives

Abstract

Phenylketonuria (PKU) is an inborn error of phenylalanine (phe) and tyrosine (tyr) metabolism. It is an
autosomal recessive disease occurred due to deficiency of liver enzyme phenylalanine hydroxylase (PAH).
Hence, phe is not converted to tyr and phe is accumulated in the body. Phe thus channeled to alternative
routes of metabolism and forms Phenylketones excreted in urine. Early treatment is essential to prevent
mental retardation and other intellectual disabilities. Dietary treatment remains the main cornerstone to
manage PKU since last 3-4 decades. A diet low in Phe supplemented with special amino acids formulas
must be started soon after diagnosis within seven days of life. Inspite of good results obtained from dietary
treatment in PKU, still there are some issues with palatability of the dietary formulations. There are also
issues of nutritional deficiencies of vitamins like calcitriol and cobalamin (B12). Poor cognitive and executive
functions have been observed in patients who do not follow proper dietary treatment. Attempts have also
been made to increase the palatability of food under dietary management. Role of large neutral amino acids
(LNAAs) and glycomacropeptides (GMP; found in bovine milk) as a newer dietary management have also
been explored. In recent era, advances occurred in terms of genetic therapy and enzyme replacement therapy
which opened a new door towards management of PKU. In this review, various treatment aspects of PKU
are discussed and explored.